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Evidence that serum potassium is not the etiological agent in ventricular fibrillation following coronary artery occlusion
Evidence That Serum Potassium Is Not the Etiological Agent in Ventricular
Fibrillation
Jack Wexler, M.D.,
Following
Coronary Artery
and Howard H. Patt, M.D.,
Baltimore,
Occlusion Md.
In 1839, Blake’ injected potassium carbonate into the jugular vein of dogs and observed that the animals died within 45 seconds after the injection. He concluded that death was the result of the direct action of potassium on the heart. In 1883, Ringer2 reported the interrelationships of sodium, potassium, and calcium on the contractions of the heart of ,the frog and noted failure of the heartbeat when a potassium solution was used alone. In 1895, Langendorf3 demonstrated on the mammalian heart that potassium was a heart poison and caused cardiac arrest. Wide acceptance was gained for the concept of “potassium inhibition,” in which arrest of the heart in diastole occurs when the heart is perfused by fluid containing a higher than normal concentration of potassium or abnormally low concentration of calcium and normal concentration of potassium. Support for the effect of potassium on the heart was provided by work from many laboratories in the years that followed, and in 1956, Effler and co-workers4 used potassium citrate to produce temporary cardiac arrest during cardiac surgery in man. On the other hand, an arrhythmia which simulates ventricular fibrillation has been reported to occur after the intravenous injections of potassium in doses smaller than those necessary to produce cardiac arrest. Such “paradoxical action of potassium,” although first observed in 1864, was studied and clarified by Wiggers5 in 1930. More recently, Harris and associates6 attributed an excitant action to potassium in ventricular fibrillation complicating coronary artery ligation in dogs. In this report, an elevation of serum potassium in the blood draining the infarcted myocardium is postulated as acting as an excitant on the remaining normal myocardium, with the production of ventricular fibrillation. This point of view was supported by Cherbakoff and associates,7s8 who sampled coronary sinus blood through a Cournand catheter. They correlated ventricular extrasystoles, tachycardia, and fibrillation which followed coronary artery ligation with rising levels of potassium in the coronary sinus blood. In animals pretreated From the Departments of Surgery and Medicine, Sinai Hospital of Baltimore. Inc., Baltimore, Md. This work was supported by Grant H-3265 from the National Heart Institute, National Institutes of Health, Department of Health, Education. and Welfare, Bethesda, Md. Received for publication Feb. 8, 1960. 618
Volume 60 Number 4
ROLE
OF SERUM
K IN VF AFTER
CORONARY
ARTERY
OCCLUSION
619
with insulin and glucose or sodium bicarbonate, these phenomena were sometimes delayed. This delay was correlated with stable or low levels of potassium in the coronary sinus blood. With recent increased use of potassium salts in the treatment of cardiac arrhythmias, especially those complicating digitalis toxicity (Lown and Levine.g Sampson and co-workerslOJ1) an d s t a t es of potassium depletion, it was felt that an attempt to clarify or reconcile the inhibitory, paradoxical, and excitant actions of potassium would be of practical importance. This report will deal with the results of 83 experiments on dogs in which various constituents of coronary sinus blood were studied after ligation of the left anterior descending coronary artery (LAD). Our results do not support. au excitant role for potassium in ventricular fibrillation. It is the purpose of this report to present evidence that it is unnecessary to assume an excitant role for potassium in order to explain the observation of the elevated serum potassium in some cases of ventricular fibrillation in dogs. Such an assumption may rnisdirect therapeutic efforts to prevent or abolish this serious arrhythmia which is :1 common cause of death following coronary occlusion. METHODS
1. Mongrel dogs under pentobarbital-sodium anesthesia were maintained on 95 per cent oxygen and 5 per cent carbon dioxide with an Emerson respirator. The heart was exposed through the right chest and the LAD dissected free from its accompanying vein. A ligature was placed around the LAD but not tied until control blood samples were drawn from the coronary sinus and the femoral artery. 2. Samples of blood from the coronary sinus were obtained by free flow without suction, through an indwelling polyethylene tube with a stainless steel obturator. The tube and obturator were inserted through an incision in the right atrium which was closed with a purse-string suture. The tube was inserted through the coronary sinus ostium for a distance of 4 to 5 cm. to prevent contamination with auricular blood. In some instances, a ligature was placed around the coronary sinus and tube after proper placement of the tube in the coronary sinus. 3. Serial electrocardiographic tracings were recorded throughout each experiment until the onset of ventricular fibrillation or until the end of the experimental period of 2 to 3 hours. 4. Concentrations of serum potassium were determined with a flame photometer. 5. Blood samples were drawn at various intervals after ligation of LAD from 1 minute to 3 hours. Experiments were terminated when ventricular fibrillation occurred, or if normal sinus rhythm was present for 2 to 3 hours after the ligation of LAD. RESULTS
1. Ventricular Fibrillation and Cardiac Standstill After Coronary Artery Ldgation.-A total of 83 successful ligations of a major coronary artery were performed. Of this number, 2.5 dogs (30 per cent) developed ventricular fibrillation during the period of observation, 3 (4 per cent) developed cardiac arrest, and 55 (66 per cent) maintained a normal sinus rhythm throughout the experimental period, which did not exceed 3 hours. In 13 of the 25 experiments in which ventricular fibrillation occurred and in 1 of 3 experiments in which cardiac standstill developed, it was not possible to obtain adequate samples of coronary sinus blood after the coronary artery had been ligated. This failure in some instances was due to technical difficulties, and
620
WEXLER
AND
PATT
Am. Heart J. October, 1960
in others to the very early onset of ventricular fibrillation. These experiments will not be considered further; thus, there was a total of 12 satisfactory experiments in which ventricular fibrillation occurred 1 to 30 minutes after major coronary artery ligation, and 2 in which cardiac sta‘ndstill resulted 10 and 25 minutes after ligation. TABLE I.
TWENTY-THREE DOGS WITH SIGNIFICANT INCREASE IN POTASSIUM IN THE CORONARY SINUS AFTER CORONARY ARTERY LIGATION
DOG NUMBER
zs:
60. 65. 66.
;30. ;1821 95:
INCREASEINFEMORAL INCREASEIN CORONARY SINUS POTASSIUM(MEQ.) A.RTERY POTASSIUM(MEQ.) 0.7 0.9 0.6 0.5 0.6 0.6 0.6 1.1 0.5 1.3 1.3 1.4 2.4 1.1 0.6 3.5 1.2 0.5 2.1 0.6 2.6 2.3 1.4
’
1.0 1.1 0.4 0.1 0.5 0.6 0.3 1.6 0.3 0.3 1.4 0.3 Decrease 1.4 0.5 2.5 0.4 1.j 1.9 0.2 Decrease 2”s
CARDIAC RHYTHM NSR NSR NSR NSR NSR NSR NSR NSR NSR Vent. Fib. NSR Vent. Fib. Vent. Fib. NSR NSR NSR NSR NSR NSR NSR Asystole Asystole NSR
2. Changes in Coronary Sinus and Femoral Artery Serum Potassium After Coronary Artery Ligation.-Only 23 of 69 animals (33 per cent) in which it was possible to obtain serial samples from the coronary sinus showed a significant increase in coronary sinus potassium of 0.5 mEq./liter or more. Thirteen of these 23 showed an increase in the concentration of potassium in the femoral artery, whereas 10 of these 23 showed no such increase. In 2 instances, a decrease in the concentration of potassium in the femoral artery was observed during the sampling period, which extended for a maximum of 3 hours (Table I). 3. Twenty-Three Experiments With Elevation of Potassium in the Coronary Sinus After Coronary Artery Ligation.-Eighteen (78 per cent) of the 23 animals which showed an elevation of potassium in the coronary sinus maintained normal sinus rhythm throughout the experiment (Table I and Fig. 1). Three (13 per cent) of the 23 which showed an elevation of potassium in the coronary sinus terminated in ventricular fibrillation, and these did not show a significant increase in the level of potassium in the femoral artery (Table I and Fig. 1). Two (9 per cent) terminated in cardiac standstill, and one of these showed a definite increase in potassium in the femoral artery of 3.4 mEq. above the control 1 minute before asystole.
EtEr“4” ROLE
OF SERUM K IN VF AFTER CORONARY .%RTERY OCCLUSION
621
4. Forty-Six Experiments Without Elevation of Potassium in the Coronary Sinus After Coronary Artery Ligation.-Thirty-seven (80 per cent) of the 46 animals which did not show an elevated level of potassium in the coronary sinus maintained normal sinus rhythm throughout the experimental period (Fig. 1 1. Nine (20 per cent) terminated in ventricular fibrillation (Fig. 1). 5. Coronary Sinus Flow After Onset of l’entricular Fibrillation.-In 5 animals a free flow of blood continued from the indwelling coronary sinus tube for 1 to 2 minutes after the onset of ventricular fibrillation. Two of these 5 animals showed an increase of 3.0 and 2.5 mEq./liter above control levels for the coronary sinus, 1 an increase of 0.4 mEq./liter, and the other 2 showed no change in potassium. 75%
VENTRICULAR FIBRILLATION 02 dew
Fig. l.-Lack
NORMAL SINUS RHYTHM ,66 dogal
of relationship between elevated levels of potassium in the coronary sinus and cardiac rhythm.
DISCUSSION
The occurrence of small but definite free flow from the coronary sinus for 1 to 2 minutes after the onset of ventricular fibrillation was a surprising finding. Studies are under way to determine the cause of this flow of blood. The elevation of potassium in the femoral artery which was observed in some experiments was probably the result of a combination of causes. Potassium lost from damaged myocardial cellsr2J6 may have contributed to the total intravascular pool of potassium. In addition, tissue anoxia secondary to hemodynamic disturbances which resulted from the myocardial infarction may’ have caused a loss of potassium from skeletal muscle and other body tissue.‘“-15 In only 23 of 69 of our experiments (33 per cent) were we able to demonstrate an elevation of potassium in the coronary sinus blood following coronary artery ligation. This is contrary to claims of an increase in the potassium in coronar? sinus blood reported in the literature. 6,7 Furthermore, only 3 (13 per cent 1 of
622
WEXLER
AND
Am. Heart J. October, 1960
PATT
the animals which showed an elevated level of potassium in coronary sinus blood developed ventricular fibrillation, whereas 9 (20 per cent) animals which failed to show an elevation in potassium in coronary sinus blood developed ventricular fibrillation. Finally, 18 animals with an average elevation of 1 mEq./ liter of potassium in coronary sinus blood maintained a normal sinus rhythm* throughout the experimental period. These results indicate that there is no consistent relationship between potassium in the coronary sinus or that in the femoral artery and ventricular fibrillation, and, therefore, the view that serum potassium is responsible for initiating fibrillation is not tenable. The elevation of potassium sometimes observed in coronary sinus blood most likely reflects the loss of potassium from the anoxic myocardial cells. Ability to demonstrate this shift in potassium would depend, therefore, on the adequacy of collateral circulation in flushing out the potassium lost from the damaged cells into the extracellular fluid and hence into the blood. Any arrhythmia observed under these conditions would more likely be related to the altered potassium gradient between the myocardial cells, depleted of potassium as a result of anoxia, and the interstitial fluid potassium, rather than to any direct stimulating or excitant action of potassium lost into the blood stream.17J8 Infusion of potassium may produce effects similar to intracellular depletion of potassium by temporarily reducing the normal potassium gradient of 3O:l (intracellular potassium to extracellular potassium). It is hoped that a more rational approach to the prevention and possibly the treatment of ventricular fibrillation will result from the clear realization that elevation of the level of potassium in coronary sinus blood, when observed after LAD ligation, is the result of myocardial depletion of potassium. This potassium is not the initiating factor of ventricular fibrillation complicating coronary artery occlusion, although the myocardial depletion of potassium may be. Therefore, therapeutic efforts should not be aimed at lowering serum potassium, but rather at seeking means to prevent loss of potassium from the myocardium or to shift potassium back into the myocardial cells. SUMMARY
1. Elevation of the concentration of potassium in the coronary sinus occurred only in 33 per cent of 69 dogs after ligation of a major coronary artery. 2. Eighteen of the 23 dogs (78 per cent) with an elevation of the level of potassium in the coronary sinus blood maintained a normal sinus rhythm throughout the experimental period. 3. Of 12 animals which developed ventricular fibrillation after coronary artery ligation, only 3 showed a significant elevation of the concentration of potassium in the coronary sinus. The other 9 failed to show any increase in the level of potassium in the coronary sinus. None of the 12 showed an increase in the concentration of potassium in the femoral artery. 4. These results fail to support the thesis that an increase in the levels of serum potassium incites ventricular fibrillation after coronary artery ligation. *Occasional
premature
ventricular
beats were observed
early
ligation
in
of the animals.
ic%E“4” ROLE
OF SERUM
K IN
VF i\FTER
CORONARY
,iRTERY
OCCLUSION
623
We wish to thank Mr. Doward B. Patterson, Jr., For his technical assistance in the perCor~n,rnce of the blood analyses. REFERENCES
1.
8.
Blake, J.: Observations on the Physiologic Effects of Various Agents Introduced Into the C;rrllt&on Fainburg Med. & Surg. J. 51:330, 1839. Ringer, S.: A Furthe] r Contribution Regarding the Influence of Different Constituents of the Blood on th le Contraction of the Heart, J. Physiol. 4:29, 1883. Langendorf, 0.: Die Reaktion des Hermuskels auf Dauerreize, Arch. f. d. ges. Physiol. 61:291, lPO< .. . . Effler. D. B.. CGroves, L. K., and Sones, F. M.: Elective Cardiac Arrest in Open-IIeart 3leveland ‘Surgery, C.-. _.-. -- Clin. -..--_ Ouart. 23110.5. 19.56. Wiggers, C. J.: Studies on Ven~~~~~a;ib;;ilation Produced by Electric Shock. III. The Action of Antagonistic Salts, Am. J. Physiol. 93:197, 1930. Harris, A. S., Bisteni, A., Russell, R. A., Brigham, J. C., and Firestone, J. E.: Excitatory Factors in Ventricular Tachycardia Resulting From Myocardial Ischemia: Potassium, a Major Excitant, Science 119:200, 1954. Cherbakoff, A., Toyama, S., and HamilCon, W. F.: Relation Between Coronary Sinus Plasma Potassium and Cardiac Arrhvthmia. Circulation Res. 5:517. 1957. Cherbakoff, A., and Toyama, S.: Acute Hypokalemia and Ventricular Fibrillation, Fed. I’roc.
9.
Lown,
-...,U.u..“..)
2. 3.
4. 5. 6. 7.
--,
15:35, 1956.
B., and Levine, H. D.: Atria1 Arrhythmias, Digitalis, and Potassium, New York, 1958, Landsberger Medical Books, Inc. 10. Sampson, J. J., Alberton, E. C., and Kondo, B.: The Effect on Man of Potassium Administration in Relation to Digitalis Glycosides, With Special Reference to Blood Serum Potassium, the Electrocardiogram and Ectopic Beats, AM. HEART J. 6:164, 1943. 11. Sampson, J. J., and Anderson, E. M.: The Treatment of Certain Cardiac Arrhythmias With Potassium Salts, J.A.M.A. 99:2257, 1932. 12. Myers, V. C., and Mangun, G. H.: Some Chemical Observations on the Human Heart in Health and Disease, J. Lab. & Ciin. Med. 26:199, 1940. 13. Harrison, T.: Studies in Congestive Heart Failure; Potassium Content of Skeletal and Cardiac Muscle, J. Clin. Invest. 8:325, 1930. 14. Wilkins, W. E., and CuIIen, G. E.: Electrolytes in Uuman Tissue. III. A Comparison of y90r3mal Hearts Wrth Hearts Showing Congestive Farlure, J. Clirr. Invest. I2:1063, 1.5. Cullen, G. ‘E., and Wilkins, W. E.: Electrolytes in Human Tissue-Digestion of Tissue and Other Biological Material and Subsequent Determination of Various Electrolytes. J. Biol. Chem. 102:403, 1933. 16. Jennings, R. A., Crant, R., and Smetten, G. W.: Studies in Distribution and Localization of Potassium in Early Myocardial Ischemic Injury, A.M.A. Arch. Path. 63:586, 1957. 17. Murphy, Q. R., editor: Metabolic Aspects of Transport Across Cell Membranes, Madison, 1957, University of Wisconsin Press, pp. 115-123. 18. Weidmann, S.: Resting and Action Potentials of Cardiac Muscle, Ann. New York .I\(.atl. SC. 65:663, 1957.
Fibrillation
Jack Wexler, M.D.,
Following
Coronary Artery
and Howard H. Patt, M.D.,
Baltimore,
Occlusion Md.
In 1839, Blake’ injected potassium carbonate into the jugular vein of dogs and observed that the animals died within 45 seconds after the injection. He concluded that death was the result of the direct action of potassium on the heart. In 1883, Ringer2 reported the interrelationships of sodium, potassium, and calcium on the contractions of the heart of ,the frog and noted failure of the heartbeat when a potassium solution was used alone. In 1895, Langendorf3 demonstrated on the mammalian heart that potassium was a heart poison and caused cardiac arrest. Wide acceptance was gained for the concept of “potassium inhibition,” in which arrest of the heart in diastole occurs when the heart is perfused by fluid containing a higher than normal concentration of potassium or abnormally low concentration of calcium and normal concentration of potassium. Support for the effect of potassium on the heart was provided by work from many laboratories in the years that followed, and in 1956, Effler and co-workers4 used potassium citrate to produce temporary cardiac arrest during cardiac surgery in man. On the other hand, an arrhythmia which simulates ventricular fibrillation has been reported to occur after the intravenous injections of potassium in doses smaller than those necessary to produce cardiac arrest. Such “paradoxical action of potassium,” although first observed in 1864, was studied and clarified by Wiggers5 in 1930. More recently, Harris and associates6 attributed an excitant action to potassium in ventricular fibrillation complicating coronary artery ligation in dogs. In this report, an elevation of serum potassium in the blood draining the infarcted myocardium is postulated as acting as an excitant on the remaining normal myocardium, with the production of ventricular fibrillation. This point of view was supported by Cherbakoff and associates,7s8 who sampled coronary sinus blood through a Cournand catheter. They correlated ventricular extrasystoles, tachycardia, and fibrillation which followed coronary artery ligation with rising levels of potassium in the coronary sinus blood. In animals pretreated From the Departments of Surgery and Medicine, Sinai Hospital of Baltimore. Inc., Baltimore, Md. This work was supported by Grant H-3265 from the National Heart Institute, National Institutes of Health, Department of Health, Education. and Welfare, Bethesda, Md. Received for publication Feb. 8, 1960. 618
Volume 60 Number 4
ROLE
OF SERUM
K IN VF AFTER
CORONARY
ARTERY
OCCLUSION
619
with insulin and glucose or sodium bicarbonate, these phenomena were sometimes delayed. This delay was correlated with stable or low levels of potassium in the coronary sinus blood. With recent increased use of potassium salts in the treatment of cardiac arrhythmias, especially those complicating digitalis toxicity (Lown and Levine.g Sampson and co-workerslOJ1) an d s t a t es of potassium depletion, it was felt that an attempt to clarify or reconcile the inhibitory, paradoxical, and excitant actions of potassium would be of practical importance. This report will deal with the results of 83 experiments on dogs in which various constituents of coronary sinus blood were studied after ligation of the left anterior descending coronary artery (LAD). Our results do not support. au excitant role for potassium in ventricular fibrillation. It is the purpose of this report to present evidence that it is unnecessary to assume an excitant role for potassium in order to explain the observation of the elevated serum potassium in some cases of ventricular fibrillation in dogs. Such an assumption may rnisdirect therapeutic efforts to prevent or abolish this serious arrhythmia which is :1 common cause of death following coronary occlusion. METHODS
1. Mongrel dogs under pentobarbital-sodium anesthesia were maintained on 95 per cent oxygen and 5 per cent carbon dioxide with an Emerson respirator. The heart was exposed through the right chest and the LAD dissected free from its accompanying vein. A ligature was placed around the LAD but not tied until control blood samples were drawn from the coronary sinus and the femoral artery. 2. Samples of blood from the coronary sinus were obtained by free flow without suction, through an indwelling polyethylene tube with a stainless steel obturator. The tube and obturator were inserted through an incision in the right atrium which was closed with a purse-string suture. The tube was inserted through the coronary sinus ostium for a distance of 4 to 5 cm. to prevent contamination with auricular blood. In some instances, a ligature was placed around the coronary sinus and tube after proper placement of the tube in the coronary sinus. 3. Serial electrocardiographic tracings were recorded throughout each experiment until the onset of ventricular fibrillation or until the end of the experimental period of 2 to 3 hours. 4. Concentrations of serum potassium were determined with a flame photometer. 5. Blood samples were drawn at various intervals after ligation of LAD from 1 minute to 3 hours. Experiments were terminated when ventricular fibrillation occurred, or if normal sinus rhythm was present for 2 to 3 hours after the ligation of LAD. RESULTS
1. Ventricular Fibrillation and Cardiac Standstill After Coronary Artery Ldgation.-A total of 83 successful ligations of a major coronary artery were performed. Of this number, 2.5 dogs (30 per cent) developed ventricular fibrillation during the period of observation, 3 (4 per cent) developed cardiac arrest, and 55 (66 per cent) maintained a normal sinus rhythm throughout the experimental period, which did not exceed 3 hours. In 13 of the 25 experiments in which ventricular fibrillation occurred and in 1 of 3 experiments in which cardiac standstill developed, it was not possible to obtain adequate samples of coronary sinus blood after the coronary artery had been ligated. This failure in some instances was due to technical difficulties, and
620
WEXLER
AND
PATT
Am. Heart J. October, 1960
in others to the very early onset of ventricular fibrillation. These experiments will not be considered further; thus, there was a total of 12 satisfactory experiments in which ventricular fibrillation occurred 1 to 30 minutes after major coronary artery ligation, and 2 in which cardiac sta‘ndstill resulted 10 and 25 minutes after ligation. TABLE I.
TWENTY-THREE DOGS WITH SIGNIFICANT INCREASE IN POTASSIUM IN THE CORONARY SINUS AFTER CORONARY ARTERY LIGATION
DOG NUMBER
zs:
60. 65. 66.
;30. ;1821 95:
INCREASEINFEMORAL INCREASEIN CORONARY SINUS POTASSIUM(MEQ.) A.RTERY POTASSIUM(MEQ.) 0.7 0.9 0.6 0.5 0.6 0.6 0.6 1.1 0.5 1.3 1.3 1.4 2.4 1.1 0.6 3.5 1.2 0.5 2.1 0.6 2.6 2.3 1.4
’
1.0 1.1 0.4 0.1 0.5 0.6 0.3 1.6 0.3 0.3 1.4 0.3 Decrease 1.4 0.5 2.5 0.4 1.j 1.9 0.2 Decrease 2”s
CARDIAC RHYTHM NSR NSR NSR NSR NSR NSR NSR NSR NSR Vent. Fib. NSR Vent. Fib. Vent. Fib. NSR NSR NSR NSR NSR NSR NSR Asystole Asystole NSR
2. Changes in Coronary Sinus and Femoral Artery Serum Potassium After Coronary Artery Ligation.-Only 23 of 69 animals (33 per cent) in which it was possible to obtain serial samples from the coronary sinus showed a significant increase in coronary sinus potassium of 0.5 mEq./liter or more. Thirteen of these 23 showed an increase in the concentration of potassium in the femoral artery, whereas 10 of these 23 showed no such increase. In 2 instances, a decrease in the concentration of potassium in the femoral artery was observed during the sampling period, which extended for a maximum of 3 hours (Table I). 3. Twenty-Three Experiments With Elevation of Potassium in the Coronary Sinus After Coronary Artery Ligation.-Eighteen (78 per cent) of the 23 animals which showed an elevation of potassium in the coronary sinus maintained normal sinus rhythm throughout the experiment (Table I and Fig. 1). Three (13 per cent) of the 23 which showed an elevation of potassium in the coronary sinus terminated in ventricular fibrillation, and these did not show a significant increase in the level of potassium in the femoral artery (Table I and Fig. 1). Two (9 per cent) terminated in cardiac standstill, and one of these showed a definite increase in potassium in the femoral artery of 3.4 mEq. above the control 1 minute before asystole.
EtEr“4” ROLE
OF SERUM K IN VF AFTER CORONARY .%RTERY OCCLUSION
621
4. Forty-Six Experiments Without Elevation of Potassium in the Coronary Sinus After Coronary Artery Ligation.-Thirty-seven (80 per cent) of the 46 animals which did not show an elevated level of potassium in the coronary sinus maintained normal sinus rhythm throughout the experimental period (Fig. 1 1. Nine (20 per cent) terminated in ventricular fibrillation (Fig. 1). 5. Coronary Sinus Flow After Onset of l’entricular Fibrillation.-In 5 animals a free flow of blood continued from the indwelling coronary sinus tube for 1 to 2 minutes after the onset of ventricular fibrillation. Two of these 5 animals showed an increase of 3.0 and 2.5 mEq./liter above control levels for the coronary sinus, 1 an increase of 0.4 mEq./liter, and the other 2 showed no change in potassium. 75%
VENTRICULAR FIBRILLATION 02 dew
Fig. l.-Lack
NORMAL SINUS RHYTHM ,66 dogal
of relationship between elevated levels of potassium in the coronary sinus and cardiac rhythm.
DISCUSSION
The occurrence of small but definite free flow from the coronary sinus for 1 to 2 minutes after the onset of ventricular fibrillation was a surprising finding. Studies are under way to determine the cause of this flow of blood. The elevation of potassium in the femoral artery which was observed in some experiments was probably the result of a combination of causes. Potassium lost from damaged myocardial cellsr2J6 may have contributed to the total intravascular pool of potassium. In addition, tissue anoxia secondary to hemodynamic disturbances which resulted from the myocardial infarction may’ have caused a loss of potassium from skeletal muscle and other body tissue.‘“-15 In only 23 of 69 of our experiments (33 per cent) were we able to demonstrate an elevation of potassium in the coronary sinus blood following coronary artery ligation. This is contrary to claims of an increase in the potassium in coronar? sinus blood reported in the literature. 6,7 Furthermore, only 3 (13 per cent 1 of
622
WEXLER
AND
Am. Heart J. October, 1960
PATT
the animals which showed an elevated level of potassium in coronary sinus blood developed ventricular fibrillation, whereas 9 (20 per cent) animals which failed to show an elevation in potassium in coronary sinus blood developed ventricular fibrillation. Finally, 18 animals with an average elevation of 1 mEq./ liter of potassium in coronary sinus blood maintained a normal sinus rhythm* throughout the experimental period. These results indicate that there is no consistent relationship between potassium in the coronary sinus or that in the femoral artery and ventricular fibrillation, and, therefore, the view that serum potassium is responsible for initiating fibrillation is not tenable. The elevation of potassium sometimes observed in coronary sinus blood most likely reflects the loss of potassium from the anoxic myocardial cells. Ability to demonstrate this shift in potassium would depend, therefore, on the adequacy of collateral circulation in flushing out the potassium lost from the damaged cells into the extracellular fluid and hence into the blood. Any arrhythmia observed under these conditions would more likely be related to the altered potassium gradient between the myocardial cells, depleted of potassium as a result of anoxia, and the interstitial fluid potassium, rather than to any direct stimulating or excitant action of potassium lost into the blood stream.17J8 Infusion of potassium may produce effects similar to intracellular depletion of potassium by temporarily reducing the normal potassium gradient of 3O:l (intracellular potassium to extracellular potassium). It is hoped that a more rational approach to the prevention and possibly the treatment of ventricular fibrillation will result from the clear realization that elevation of the level of potassium in coronary sinus blood, when observed after LAD ligation, is the result of myocardial depletion of potassium. This potassium is not the initiating factor of ventricular fibrillation complicating coronary artery occlusion, although the myocardial depletion of potassium may be. Therefore, therapeutic efforts should not be aimed at lowering serum potassium, but rather at seeking means to prevent loss of potassium from the myocardium or to shift potassium back into the myocardial cells. SUMMARY
1. Elevation of the concentration of potassium in the coronary sinus occurred only in 33 per cent of 69 dogs after ligation of a major coronary artery. 2. Eighteen of the 23 dogs (78 per cent) with an elevation of the level of potassium in the coronary sinus blood maintained a normal sinus rhythm throughout the experimental period. 3. Of 12 animals which developed ventricular fibrillation after coronary artery ligation, only 3 showed a significant elevation of the concentration of potassium in the coronary sinus. The other 9 failed to show any increase in the level of potassium in the coronary sinus. None of the 12 showed an increase in the concentration of potassium in the femoral artery. 4. These results fail to support the thesis that an increase in the levels of serum potassium incites ventricular fibrillation after coronary artery ligation. *Occasional
premature
ventricular
beats were observed
early
ligation
in
of the animals.
ic%E“4” ROLE
OF SERUM
K IN
VF i\FTER
CORONARY
,iRTERY
OCCLUSION
623
We wish to thank Mr. Doward B. Patterson, Jr., For his technical assistance in the perCor~n,rnce of the blood analyses. REFERENCES
1.
8.
Blake, J.: Observations on the Physiologic Effects of Various Agents Introduced Into the C;rrllt&on Fainburg Med. & Surg. J. 51:330, 1839. Ringer, S.: A Furthe] r Contribution Regarding the Influence of Different Constituents of the Blood on th le Contraction of the Heart, J. Physiol. 4:29, 1883. Langendorf, 0.: Die Reaktion des Hermuskels auf Dauerreize, Arch. f. d. ges. Physiol. 61:291, lPO< .. . . Effler. D. B.. CGroves, L. K., and Sones, F. M.: Elective Cardiac Arrest in Open-IIeart 3leveland ‘Surgery, C.-. _.-. -- Clin. -..--_ Ouart. 23110.5. 19.56. Wiggers, C. J.: Studies on Ven~~~~~a;ib;;ilation Produced by Electric Shock. III. The Action of Antagonistic Salts, Am. J. Physiol. 93:197, 1930. Harris, A. S., Bisteni, A., Russell, R. A., Brigham, J. C., and Firestone, J. E.: Excitatory Factors in Ventricular Tachycardia Resulting From Myocardial Ischemia: Potassium, a Major Excitant, Science 119:200, 1954. Cherbakoff, A., Toyama, S., and HamilCon, W. F.: Relation Between Coronary Sinus Plasma Potassium and Cardiac Arrhvthmia. Circulation Res. 5:517. 1957. Cherbakoff, A., and Toyama, S.: Acute Hypokalemia and Ventricular Fibrillation, Fed. I’roc.
9.
Lown,
-...,U.u..“..)
2. 3.
4. 5. 6. 7.
--,
15:35, 1956.
B., and Levine, H. D.: Atria1 Arrhythmias, Digitalis, and Potassium, New York, 1958, Landsberger Medical Books, Inc. 10. Sampson, J. J., Alberton, E. C., and Kondo, B.: The Effect on Man of Potassium Administration in Relation to Digitalis Glycosides, With Special Reference to Blood Serum Potassium, the Electrocardiogram and Ectopic Beats, AM. HEART J. 6:164, 1943. 11. Sampson, J. J., and Anderson, E. M.: The Treatment of Certain Cardiac Arrhythmias With Potassium Salts, J.A.M.A. 99:2257, 1932. 12. Myers, V. C., and Mangun, G. H.: Some Chemical Observations on the Human Heart in Health and Disease, J. Lab. & Ciin. Med. 26:199, 1940. 13. Harrison, T.: Studies in Congestive Heart Failure; Potassium Content of Skeletal and Cardiac Muscle, J. Clin. Invest. 8:325, 1930. 14. Wilkins, W. E., and CuIIen, G. E.: Electrolytes in Uuman Tissue. III. A Comparison of y90r3mal Hearts Wrth Hearts Showing Congestive Farlure, J. Clirr. Invest. I2:1063, 1.5. Cullen, G. ‘E., and Wilkins, W. E.: Electrolytes in Human Tissue-Digestion of Tissue and Other Biological Material and Subsequent Determination of Various Electrolytes. J. Biol. Chem. 102:403, 1933. 16. Jennings, R. A., Crant, R., and Smetten, G. W.: Studies in Distribution and Localization of Potassium in Early Myocardial Ischemic Injury, A.M.A. Arch. Path. 63:586, 1957. 17. Murphy, Q. R., editor: Metabolic Aspects of Transport Across Cell Membranes, Madison, 1957, University of Wisconsin Press, pp. 115-123. 18. Weidmann, S.: Resting and Action Potentials of Cardiac Muscle, Ann. New York .I\(.atl. SC. 65:663, 1957.